Liver transporters

Cholesterol is biosynthesized in the liver, transported throughout the body to be used in a variety of ways, and returned to the liver where it serves as the biosynthetic precursor to other steroids. But cholesterol is a lipid and isn t soluble in water. How can it move through the blood if it doesn t dissolve in it The answer is that it doesn t dissolve, but is instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein). 

Liver Liver is the major organ for metabolism of almost all amino acids the exception is the branched-chain amino acids which are metabolised in muscle and adipose tissue (see Chapter 8). Of the amino acids absorbed from the lumen of the intestine in the adult, at least 70% are metabolised in the liver. Transporters for almost all amino acids are, therefore, very active in the membranes of hepatocytes. 

Feces collection return the mice to their respective cages and collect feces for 24 h (see Note 3). Longer collection times have the potential to underestimate absorption since some absorbed cholesterol will end up in HDL and subsequently be taken up by the liver, transported to the bile, and secreted into the intestine. However, semi-purified diets are usually very low in fiber, which may reduce intestinal motility. If necessary, sterol transit time is measured in a preliminary experiment where only radiolabeled phytosterol is given and total fecal output is collected on days 1, 2, and 3. Sterols are quantitatively extracted (see below Section 3.1.3) and the time for 90% excretion determined. 

The paradigm emerging is that of a cascade (a series of biochemical steps using secondary, tertiary, or more messenger molecules, each successive step amplifying those of the preceding step). After retinoid absorption from the gut, biotransformation in the liver, transport through the blood and across the... 

Wehner, F., Kirme, R.K., and Petzinger, E. (1996) Second International Ringberg Conference Cell Biology and Molecular Basis of Liver Transport . Hepatology, 24, 259-267. 

Liver is the principal site of D-fructose metabolism. D-Fructose is transported to the liver from the small intestine by way of the portal blood-vessel. Experiments with perfused pig and rat livers revealed that the rate of elimination of D-fructose from blood is a function of the sugar concentration,26,27 and follows Michaelis-Menten kinetics.27,28 Carrier-mediated, liver-membrane transport of D-fructose has a high29 Km and Vmax, in comparison to the intracellular phosphorylation constants of D-fructose in both pigeon and rat livers.27,28 For example, the calculated rat-liver transport for D-fructose has a Km of 67 mM and a Vmax of 30 /u,mole.min. g-1, in contrast to the lower, calculated fruc-tokinase Km of 1.0 mM and Vmax of 10.3 pmole. min r1. g 1 with D-fruc-tose and Km of 0.54 mM with adenosine 5 -triphosphate (ATP). In perfused pig-liver,28 the transport Km for D-fructose is only ten times that of intracellular phosphorylation by fructokinase. Hence, D-fructose-transport values suggested that, at physiological D-fructose concentrations, membrane transport limits the rate of uptake, thereby protecting the liver from severe depletion of adenine nucleotide.28,29... 

Major physiological function Transports dietary triglyceride (Tg) from intestines to extrahepatic tissues (e.g., muscle, adipose tissue) Tg-depleted remnants deliver dietary cholesterol and some Tg to the liver Transports hepatic Tg to extrahepatic tissues converted into LDL Transports plasma cholesterol to liver and to extrahepatic tissues Takes up cholesterol from extrahepatic tissues and delivers it to liver, steroid-producing tissues, and other lipoproteins... 

Cyclosporine increases the systemic exposure of all statins (lovastatin, simvastatin, pravastatin, cerivastatin, and rosuvastatin), due to drug-drug interaction (via either CYPs or transporters like P-gp and OATP) in the liver. Rosuvastatin has been shown to be a substrate for the human liver transporter OATP2 and BCRP, but not P-gp. It s metabolic clearance is low and mainly mediated by CYP2C9. CsA treatment in transplant recipients increased AUCq 2h and Cmax of rosuvastatin (10 mg) by 7.1 and 10.6-fold, respectively, compared with control values, due to CsA inhibition of OATP2-mediated rosuvastatin hepatic uptake (Simonson et al., 2004). 

Very-low-density Lipoprotein (VLDL) B-100,C-I, C-ll, C-lll, E 0.95-1.006 30-80 Structurally similar to the chylomicrons, but smaller, produced in the liver, transport mainly endogenously- formed triglycerides... 

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